Submissions for variant NM_001029896.2(WDR45):c.19C>T (p.Arg7Ter)

dbSNP: rs886041382

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000272581	SCV000329918	pathogenic	not provided	2023-08-28	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25592411, 34272103, 25356899, 26790960, 26481852, 29445477, 28932395, 26173968, 25263061, 24847269, 24621584, 23687123, 23435086, 20562859, 23176820, 29981852, 31487502, 32382396, 33391346, 34374989)
Ambry Genetics	RCV000624584	SCV000740993	pathogenic	Inborn genetic diseases	2015-08-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705613	SCV000834618	pathogenic	Neurodegeneration with brain iron accumulation 5	2024-04-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg7*) in the WDR45 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WDR45 are known to be pathogenic (PMID: 23176820, 24368176, 24621584, 25744623, 26790960, 27030146, 27652284, 28554332). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurodegeneration with brain iron accumulation (PMID: 23176820, 25356899). ClinVar contains an entry for this variant (Variation ID: 280098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000272581	SCV001247589	pathogenic	not provided	2018-10-01	criteria provided, single submitter	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001255400	SCV001431800	pathogenic	Global developmental delay	2019-11-01	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV000705613	SCV002012095	pathogenic	Neurodegeneration with brain iron accumulation 5	2021-10-02	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported multiple times as an established pathogenic variant (ClinVar Id: VCV000280098.14, PMID: 32382396, 31487502). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Molecular Genetics Lab, CHRU Brest	RCV003883145	SCV004697802	pathogenic	Neurodegeneration with brain iron accumulation 5; Oculocutaneous albinism type 7		criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000705613	SCV005420677	pathogenic	Neurodegeneration with brain iron accumulation 5	2024-10-04	criteria provided, single submitter	research	PVS1,PM6,PM2